Luo, Yingzhe, Xu, Huimin, Xiong, Shaoquan et al. · Comprehensive Physiology · 2025 · DOI
This review examines how our immune system's aging process may explain the severe fatigue in ME/CFS. As immune cells age, they cause chronic inflammation that damages the energy-producing parts of our cells (mitochondria), while stress hormones and nerve signals become imbalanced. These problems across different body systems work together to create and maintain the exhaustion that defines ME/CFS.
This work offers a coherent biological explanation for ME/CFS fatigue by connecting immune aging to energy metabolism and hormone dysfunction—potentially identifying new therapeutic targets and biomarkers (cytokines, immune exhaustion markers). Understanding these cross-system interactions may shift clinical approaches from single-system treatments to integrated strategies addressing immune and metabolic dysfunction simultaneously.
This review does not prove that immunosenescence causes ME/CFS; it presents evidence for association and biological plausibility. The study cannot establish whether immunosenescence is primary or secondary to other disease processes. It also does not validate specific biomarkers or demonstrate efficacy of proposed therapeutic interventions in clinical trials.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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Primary citation
Luo, Yingzhe, Xu, Huimin, Xiong, Shaoquan, & Ke, Jianlong (2025). Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Physical Fatigue Through the Perspective of Immunosenescence.. Comprehensive Physiology. https://doi.org/10.1002/cph4.70056
BibTeX
@article{mecfsatlas-luo-2025-understanding-myalgic,
author = {Luo, Yingzhe and Xu, Huimin and Xiong, Shaoquan and Ke, Jianlong},
title = {Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Physical Fatigue Through the Perspective of Immunosenescence.},
journal = {Comprehensive Physiology},
year = {2025},
doi = {10.1002/cph4.70056},
note = {PubMed: 41017304},
url = {https://www.mecfsatlas.com/evidence/luo-2025-understanding-myalgic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/luo-2025-understanding-myalgic
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